Lithium + Antipsychotics B&B Flashcards
what psychological disorder is lithium used to treat, and what is its MOA?
bipolar disorder - not common anymore due to narrow TI
inhibits inositol monophosphate (IMPase), which regenerates inositol —> depleted inositol causes decrease in 2nd messenger levels (PIP2, IP3, DAG)
what are the risk factors for lithium toxicity? why does this make sense?
excreted renally, reabsorbed in PCT (like Na+)
therefore, risk factors for toxicity = renal insufficiency, volume depletion, elderly (low GFR)
which drugs increase vs decrease lithium levels in the body?
increase: thiazide diuretics, NSAIDS, ACE inhibitors
decrease: K+ sparing diuretics (Amiloride)
varying: loop diuretics
what are the acute, long-term, and fetal adverse effects of lithium?
acute: tremor (symmetric, usually limited to arms/hands)
long-term: hypothyroidism (goiter), nephrogenic diabetes insipidus, cardiac dysfunction (suppression of sinus node - bradycardia)
fetal: Ebstein’s anomaly (RV atrialization)
Pt w PMH of bipolar disorder presents with polyuria and polydipsia. Blood chemistry shows normal serum Na+. Urine labs show low osmolarity. Vasopressin is given by a resident to no effect. What drug should be started instead (and give MOA), and which drug should be discontinued?
dx: diabetes insipidus (tubules do not respond to ADH) due to lithium toxicity (tx bipolar)
discontinue lithium, give amiloride (K+ sparing diuretic)
amiloride: inhibits ENaC of principal cells —> this also blocks lithium entry into renal cells (blocks reabsorption)
baby born with Ebstein’s anomaly was most likely exposed to ____ in utero
lithium - completely equilibrates across the placenta
what is the result of D1 vs D2 receptor activation?
D1 receptors activate adenylyl cyclase —> increased cAMP
D2 receptors inhibit adenylyl cyclase —> decreased cAMP
what is the MOA of first gen (typical) antipsychotics?
ex: haloperidol, chlorpromazine, trifluoperazine, fluphenazine, thioridazine, pimozide
aka “neuroleptics”, depress CNS activity via D2 receptor blockade on post-synaptic neurons
D2 normally inhibits adenylyl cyclase (decrease cAMP); therefore, blocking D2 leads to increase cAMP
what are the side effects of first generation (typical) antipsychotics? 4
ex: haloperidol, chlorpromazine, trifluoperazine, fluphenazine, thioridazine, pimozide
- D2 blockade —> extrapyramidal Parkinsonism, hyperprolactinemia, amenorrhea, galactorrhea, gynecomastia, anti-emetic
- histamine blockade —> sedation, constipation
- ACh blockade —> dry mouth, constipation
- alpha1 blockade —> hypotension, ED
contrast the following extrapyramidal symptoms that occur with dopamine receptor blockage by first gen. antipsychotics, including when they occur:
a. dystonia
b. akathisia
c. bradykinesia
d. tardive dyskinesia
a. dystonia (hours/days): spasms/stiffness, tx w/ benztropine (blocks M1)
b. akathisia (days, most common): restlessness, tx w/ lower dose or benzos or propranolol
c. bradykinesia (weeks): Parkinson-like, tx w/ benztropine
d. tardive dyskinesia (months, years): choreoathetosis (smacking lips, grimacing), irreversible
what is the difference between high potency and low potency first generation (typical) antipsychotics?
name 3 high potency and 2 low potency
high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine
low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine
sort the following into high potency vs low potency first generation antipsychotics:
a. haloperidol
b. trifluoperazine
c. thioridazine
d. chlorpromazine
e. fluphenazine
high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine
low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine
which of the following antipsychotics is most likely to cause sedation?
a. trifluoperazine
b. fluphenazine
c. thioridazine
c. thioridazine - low potency
high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine
low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine
how does neuroleptic malignant syndrome (NMS) present? how is it treated?
[neuroleptics = first gen. antipsychotics]
occurs 7-10 days after tx starts w/ fever and rigid muscles, encephalopathy (mental status changes), elevated CK, myoglobinuria (rhabdomyolysis, acute renal failure)
tx: dantrolene (muscle relaxant) + bromocriptine (dopamine agonist)
which antipsychotic is most strongly associated with prolonged QT interval? what is the reason this occurs?
haloperidol
blocked cardiac K+ channels —> prolonged QT interval —> may cause Torsade de Pointes
which 2 first generation (typical) antipsychotics are associated with ocular side effects? what are the side effects, specifically?
Chlorpromazine —> Corneal deposits
thioRidazine —> Retinal deposits (“browning” vision, resembles retinitis pigmentosa)
which first generation (typical) antipsychotic is associated with corneal deposits?
Chlorpromazine —> Corneal deposits
first generation (typical) antipsychotic is associated with retinal deposits?
thioRidazine —> Retinal deposits (“browning” vision, resembles retinitis pigmentosa)
what is the difference between first generation (typical) vs second generation (atypical) antipsychotics?
second generation have fewer extrapyramidal and anti-cholinergic adverse effects
which 2 antipsychotics are most associated with metabolic syndrome?
- clozapine
- olanzapine
both are second generation (atypical)
[metabolic syndrome = weight gain + hyperglycemia + hyperlipidemia]
what are the unique side effects (2) of clozapine among second gen. antipsychotics?
- agranulocytosis - must monitor WBCs
- seizures - dose related
which antipsychotic is associated with bone marrow toxicity?
clozapine - may cause agranulocytosis, must monitor WBCs
what is the most common cause of drug-induced hyperprolactinemia?
antipsychotics - esp. risperidone, paliperidone, haloperidol, fluphenazine
dopamine blockade —> increased prolactin (disinhibited) —> amenorrhea/ gynecomastia/ galactorrhea
which antipsychotics (2) are most closely associated with drug-induced hyperprolactinemia?
[dopamine blockade —> increased prolactin]
- risperidone
- paliperidone
[also haloperidol + fluphenazine, but these are 1st gen and not chronically used anymore]
